The role and mechanism of RIPK1 in vascular endothelial dysfunction in chronic kidney disease.

Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and cardiovascular events, but the mechanism is unclear. In our study, we found elevated levels of RIPK1 in patients with CKD and cardiovascular events through bioinformation analysis. Elevated RIPK1 levels were found in serum samples of CKD patients and were associated with vascular endothelial dysfunction and renal function. We constructed the five of six nephrectomy of CKD mice model, finding that RIPK1 expressions were elevated in abdominal aorta endothelial cells. After RIPK1 inhibition and overexpression, it was found that RIPK1 could regulate the expression of endothelial nitric oxide synthase (eNOS) and cell adhesion molecule 1 (ICAM-1), and activation of inflammatory responses and endoplasmic reticulum (ER) stress. In addition, uremic toxin induced abnormal expression of RIPK1 in vitro. We observed RIPK1-mediating endothelial dysfunction and inflammation responses by ER stress pathways through gain and loss of function. In order to explore the specific mechanism, we conducted co-immunoprecipitation and expression regulation of RIPK1 and IKK, finding that RIPK1 formed complex with IKK and regulated IKK expression. In conclusion, we demonstrated that RIPK1 levels were closely associated with vascular endothelial dysfunction in patients with CKD. With uremic toxins, RIPK1 expression was elevated, which led to the activation of inflammation through the ER stress pathway, resulting in vascular endothelial injury. Besides, activation of RIPK1-IKK-NF-κB axis was a key driver of endothelial dysfunction in CKD. Our study provides a new perspective for the study of cardiovascular events in CKD.

GWAS determined genetic loci associated with callus induction in oil palm tissue culture.

KEY MESSAGE: GWAS identified six loci at 25 kb downstream of WAK2, a crucial gene for cell wall and callus formation, enabling development of a SNP marker for enhanced callus induction potential. Efficient callus induction is vital for successful oil palm tissue culture, yet identifying genomic loci and markers for early detection of genotypes with high potential of callus induction remains unclear. In this study, immature male inflorescences from 198 oil palm accessions (dura, tenera and pisifera) were used as explants for tissue culture. Callus induction rates were collected at one-, two- and three-months after inoculation (C1, C2 and C3) as phenotypes. Resequencing generated 11,475,258 high quality single nucleotide polymorphisms (SNPs) as genotypes. GWAS was then performed, and correlation analysis revealed a positive association of C1 with both C2 (R = 0.81) and C3 (R = 0.50), indicating that C1 could be used as the major phenotype for callus induction rate. Therefore, only significant SNPs (P ≤ 0.05) in C1 were identified to develop markers for screening individuals with high potential of callus induction. Among 21 significant SNPs in C1, LD block analysis revealed six SNPs on chromosome 12 (Chr12) potentially linked to callus formation. Subsequently, 13 SNP markers were identified from these loci and electrophoresis results showed that marker C-12 at locus Chr12_12704856 can be used effectively to distinguish the GG allele, which showed the highest probability (69%) of callus induction. Furthermore, a rapid SNP variant detection method without electrophoresis was established via qPCR-based melting curve analysis. Our findings facilitated marker-assisted selection for specific palms with high potential of callus induction using immature male inflorescence as explant, aiding ortet palm selection in oil palm tissue culture.

Fear of cancer recurrence in adolescent patients with malignant bone tumors: a cross-section survey.

BACKGROUND: Adolescent malignant-bone tumor patients' fear of cancer recurrence is a significant psychological issue, and exploring the influencing factors associated with fear of cancer recurrence in this population is important for developing effective interventions. This study is to investigate the current status and factors influencing fear of cancer recurrence (FCR) related to malignant bone-tumors in adolescent patients, providing evidence for future targeted mental health support and interventions. DESIGN: A cross-sectional survey. METHODS: In total, 269 adolescent malignant-bone tumor cases were treated at two hospitals in Zhejiang Province, China from January 2023 to December 2023. Patients completed a General Information Questionnaire, Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Family Hardiness Index (FHI), and a Simple Coping Style Questionnaire (SCSQ). Univariate and multivariable logistic regressions analysis were used to assess fear of cancer recurrence. RESULTS: A total of 122 (45.4%) patients experienced FCR (FoP-Q-SF ≥ 34). Logistic regression analysis analyses showed that per capita-monthly family income, tumor stage, communication between the treating physician and the patient, patient's family relationships, family hardiness a positive coping score, and a negative coping score were the main factors influencing FCR in these patients (P < 0.05). CONCLUSIONS: FCR in malignant-bone tumor adolescent patients is profound. Healthcare professionals should develop targeted interventional strategies based on the identified factors, which affect these patients; helping patients increase family hardiness, helping patients to positively adapt, and avoid negative coping styles.

G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity.

G-quadruplexes (G4s) formed by guanine-rich nucleic acids play a role in essential biological processes such as transcription and replication. Besides the >1.5 million putative G-4-forming sequences (PQSs), the human genome features >640 million single-nucleotide variations (SNVs), the most common type of genetic variation among people or populations. An SNV may alter a G4 structure when it falls within a PQS motif. To date, genome-wide PQS-SNV interactions and their impact have not been investigated. Herein, we present a study on the PQS-SNV interactions and the impact they can bring to G4 structures and, subsequently, gene expressions. Based on build 154 of the Single Nucleotide Polymorphism Database (dbSNP), we identified 5 million gains/losses or structural conversions of G4s that can be caused by the SNVs. Of these G4 variations (G4Vs), 3.4 million are within genes, resulting in an average load of >120 G4Vs per gene, preferentially enriched near the transcription start site. Moreover, >80% of the G4Vs overlap with transcription factor-binding sites and >14% with enhancers, giving an average load of 3 and 7.5 for the two regulatory elements, respectively. Our experiments show that such G4Vs can significantly influence the expression of their host genes. These results reveal genome-wide G4Vs and their impact on gene activity, emphasizing an understanding of genetic variation, from a structural perspective, of their physiological function and pathological implications. The G4Vs may also provide a unique category of drug targets for individualized therapeutics, health risk assessment, and drug development.

Biomimetic Hemostatic Powder Derived from Coacervate-Immobilized Thermogelling Copolymers.

Intrinsic hemostasis is an innate body response to prevent bleeding based on the sol-gel transition of blood. However, it is often inadequate for exceptional situations, such as acute injury and coagulation disorders, which typically require immediate medical intervention. Herein, we report the preparation of an efficient hemostatic powder, composed of tannic acid (TA), poly(ethylene glycol) (PEG), and poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) triblock copolymer (TB), for biomimetic hemostasis at the bleeding sites. TA has a high affinity for biomolecules and cells and can form coacervates with PEG driven by hydrogen bonding. TB enhances the mechanical strength and provides thermoresponsiveness. The hemostatic powder can rapidly transit into a physical and biodegradable seal on wet substrates under physiological conditions, demonstrating its promise for the generation of instant artificial clots. Importantly, this process is independent of the innate blood clotting process, which could benefit those with blood clotting disorders. This biomimetic hemostatic powder is an adaptive topical sealing agent for noncompressible and irregular wounds, which is promising for biomedical applications.

Validity and reliability of the Chinese version of the disease-related fear scale in patients with epilepsy.

OBJECTIVE: This study aims to test the validity and reliability of the Chinese version of the Disease-Related Fear Scale (D-RFS) in order to understand the experience of fear in patients with epilepsy (PWE). METHODS: The researchers obtained translation permission and followed international guidelines to develop a Chinese version of the D-RFS. A total of 609 PWE were recruited from a general tertiary hospital in Hangzhou, China, between January 2023 and June 2023. We evaluated the psychometric properties of the D-RFS, including content validity, reliability, test-retest reliability, internal consistency, and construct validity. RESULTS: Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were conducted on two separate samples with a sample size of 307 and 302. The results of EFA indicated that the scale could be divided into three dimensions, which were supported by the structure in CFA. We named the three dimensions as follows: "fear of seizure consequences", "fear of poor epilepsy management", and "fear of social restrictions", respectively. The Cronbach's alpha coefficient for the entire scale was 0.960, with a coefficient of 0.907, 0.953, and 0.917 on three dimensions. CONCLUSION: The Chinese version of the D-RFS was found to be an effective and reliable tool to measure the experience of fear in adult PWE in China. The study could lay the foundation for future investigations to explore associated factors of epilepsy-related fear and establish intervention strategies to alleviate patients' fear in clinical practice.

Reliability and validation of the Chinese version of the epilepsy surgery satisfaction questionnaire.

OBJECTIVE: To evaluate the reliability and validity the Chinese version of 19-item Epilepsy Surgery Satisfaction Questionnaire (C-ESSQ-19) in Chinese mainland patients. METHODS: Patients with epilepsy who had epilepsy surgery in our hospital one year earlier were included. Internal consistency and test-retest reliability were assessed by using Cronbach alpha and intraclass correlation coefficient (ICC). Confirmatory factor analysis was used for construct validity. Discriminant validity was assessed using receiver operating characteristic curve analysis. RESULTS: A total of 132 patients participated in our study, consisting of 59 females and 73 males. The C-ESSQ-19 yielded a median summary score of 86.5 (IQR=72.7-98.0). The Cronbach's alpha of the four domains of the C-ESSQ-19 ranged from 0.746 to 0.973. The test-retest reliability evaluated by ICC were good to excellent, ranging from 0.71 to 0.90 (P < 0.001). The C-ESSQ-19 demonstrated excellent construct validity, as indicated by the satisfactory goodness-of-fit of the data (SRMR = 0.046; CFI = 1.000). It exhibited acceptable discriminant validity for differentiating between patients excised or not (AUC = 0.72; 95% CI = 0.59-0.86) and self-rated severity of epilepsy (AUC = 0.76, 95% CI = 0.67-0.86), but poor discriminant validity for other factors, such as being seizure-free or not (AUC = 0.66, CI = 0.56-0.75), depressed or not (AUC = 0.66, 95% CI = 0.54-0.79), and self-rated disability related to seizures (AUC = 0.65, 95% CI = 0.50-0.80). CONCLUSIONS: The C-ESSQ-19 has proven to be a reliable and valid self-rated questionnaire for assessing the satisfaction of Chinese mainland epilepsy patients with surgery.

Evaluation of a new digital pediatric malnutrition risk screening tool for hospitalized children with congenital heart disease.

BACKGROUND: In a cohort of hospitalized children with congenital heart disease (CHD), a new digital pediatric malnutrition screening tool as a mobile application was validated, and its effectiveness and clinical value were determined as a prospective study. METHODS AND RESULTS: Children with CHD (n = 1125) were screened for malnutrition risk. The incidence of risk and the differences among various age groups and types of CHD were characterized. The optimal threshold for the tool to determine if there is a risk of malnutrition is score 2, while the Youden index was 79.1%, and the sensitivity and specificity were 91.2% and 87.9%, respectively. Based on such criterion, 351 children were at risk of malnutrition accounting for 31.20% of the total. Compared with the non-malnutritional risk group, the median age for the group at risk for malnutrition was younger (8.641 months [4.8, 23.1] vs. 31.589 months [12.4, 54.3], P < 0.01), and the length of stay was longer (12.000 [8.0, 17.0] vs. (8.420 [5.0, 12.0], P < 0.01]. There were significant differences in malnutrition risk among different age groups (χ2 = 144.933, P < 0.01), and children under one year of age exhibited the highest risk for malnutrition and more extended hospital stay (H = 78.085, P < 0.01). The risk of malnutrition among children with cyanotic CHD was higher than in those with non-cyanotic CHD (χ2 = 104.384, P < 0.01). CONCLUSIONS: The new digital pediatric malnutrition screening tool showed high sensitivity and specificity in children with CHD. The tool indicated that the malnutrition risk for young children and children with cyanotic or Bethesda moderate and complex CHD was higher, and the hospitalization time was longer than in the non-risk group. The tool provides a rational approach to targeted nutrition intervention and support and may improve clinical outcomes.

Jia-Wei-Kai-Xin-San Treatment Alleviated Mild Cognitive Impairment through Anti-Inflammatory and Antiapoptotic Mechanisms in SAMP8 Mice.

Background: Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimer's disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI. Methods: MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissl's/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells. Results: It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus. Conclusion: JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice.

Transitioning through adversity: Maternal experiences and post-traumatic growth in the context of infants diagnosed with esophageal atresia - A comprehensive qualitative study.

PURPOSE: This study aimed to elucidate the experiences and growth trajectories of mothers who have infants with esophageal atresia, which would contribute to our understanding of their unique nursing care requirements and support the development of personalized nursing care strategies and interventions for these critically ill infants. DESIGN AND METHODS: This study used a qualitative descriptive approach including face to face interviews with semi-structured questions. The interviews were audio-recorded and transcribed verbatim. RESULTS: Eight mothers were interviewed between November 2021 to January 2022. The mothers described two categories of care experiences: "grief" and "post-traumatic growth". Subcategories included "beginning of chaos", "facing reality", "forced mother-infant separation", "deprived life", "deepened self-knowledge", "enhanced perception of social support", and "shift in life priorities". CONCLUSIONS: The findings of this study indicated mother of infants with esophageal atresia experienced grief, and also reported growth. A better understanding of mothers' experience and positive changes may facilitate peditric nursing practice and promote mothers to attain good psychological adaptation to enable them to take good care of their children. APPLICATION TO PRACTICE: Pediatric nurses' insight into the experience of mothers caring for infants with esophageal atresia could facilitate increased physical intimacy and optimized interaction time to understand the unique personality of these infants. Collaborating with mothers could enhance nurses' comprehension of their perspectives, concerns, and needs, and could guide intervention strategies.

Optimized Antimicrobial Peptide Jelleine-I Derivative Br-J-I Inhibits Fusobacterium Nucleatum to Suppress Colorectal Cancer Progression.

Colorectal cancer (CRC) is a major health burden worldwide due to its high morbidity, mortality, and complex etiology. Fusobacterium nucleatum (Fn), a Gram-negative anaerobe found in 30% of CRC patients, promotes CRC carcinogenesis, metastasis, and chemoresistance. Effective antimicrobial treatment is an unmet need for the rising CRC burden. Antimicrobial peptides (AMPs) represent a new class of antimicrobial drugs. In our previous study, we did the structure-activity study of Jelleine-I (J-I) and identified several halogenated J-I derivatives Cl-J-I, Br-J-I, and I-J-I. To determine whether those J-I derivatives can be a new therapy for bacterial-associated CRC, here we tested the antibacterial activities of these AMPs against Fn and their effects on CRC development. We found that Br-J-I showed the highest anti-Fn activity and Br-J-I may target membrane-associated FadA for Fn membrane disruption. More importantly, Fn promoted the growth of CRC cells-derived xenograft tumors. Br-J-I suppressed Fn load, colon inflammation, and Fn-induced CRC growth. Of note, Br-J-I induced better anti-CRC effects than common antibiotic metronidazole and Br-J-I sensitized the cancer-killing effect of chemotherapy drug 5-fluorouracil. These results suggest that Br-J-I could be considered as an adjunctive agent for CRC treatment and AMPs-based combination treatment is a new strategy for CRC in the future.

Metal-Free Catalyzed Oxidation/Decarboxylative [3+2] Cycloaddition Sequences of 3-Formylchromones to Access Pyrroles with Anti-Cancer Activity.

An efficient and direct approach to pyrroles was successfully developed by employing 3-formylchromones as decarboxylative coupling partners, and facilitated by microwave irradiation. The protocol utilizes easily accessible feedstocks, a catalytic amount of DBU without any metals, resulting in high efficiency and regioselectivity. Notably, all synthesized products were evaluated against five different cancer cell lines and compound 3l selectively inhibited the proliferation of HCT116 cells with an IC50 value of 10.65 µM.

Evaluation of the knowledge, awareness, and attitudes toward epilepsy among nurses.

BACKGROUND: The standard of care provided to patients with chronic epilepsy might be affected by clinical nurses' understanding, awareness, and attitudes toward the condition. The objective of this study was to assess the knowledge, awareness, and attitudes toward chronic epilepsy among clinical nurses in the Second Affiliated Hospital of Zhejiang University School of Medicine, China. METHODS: Two hundred and thirty-eight nurses from the neurosurgery, neurology, epilepsy center, other internal medicine and other surgery department working at our hospital participated in this descriptive and cross-sectional study in 2022. The data were collected through an electronic questionnaire, which comprised four domains including demographic and clinical epilepsy-related questions, awareness of epilepsy section, 18 items for knowledge and a 15-item scale for attitudes. Mann-Whitney U tests, Kruskal-Wallis H tests, post hoc analysis, Pearson correlation analysis, and descriptive statistics were used to analyze the non-normal distribution of the dataset. RESULTS: The clinical nurses' average score on the awareness of epilepsy section was 14.93 ± 2.69 (maximum score: 20), the knowledge of epilepsy section scored 15.41 ± 2.30 (maximum score: 18), and the epilepsy attitude section scored 30.65 ± 7.40. The knowledge and awareness accuracy of the responses to the epilepsy-related questions were positively and significantly correlated (r = 0.251, p < 0.001). The multiple linear regression model found that the department (p < 0.001) and rank (p = 0.015) of nurses were independently associated with awareness toward epilepsy. Meanwhile, there was a statistically significant difference between the departments of nurses and accuracy on the Epilepsy Knowledge Scale (H = 18.340, p < 0.001). In addition, 92.77% of nurses agreed that people with chronic epilepsy have the same rights as all people. Unfortunately, over 30% of nurses maintained an uncertain attitude toward the employment, marriage, and emotion related to epilepsy. CONCLUSION: Our findings revealed that nurses had a general awareness and understanding of epilepsy, attitudes toward epilepsy. Specifically, nurses working in the Neurology Department and the Epilepsy Center were predisposed to have a considerably better level of awareness and knowledge of epilepsy. Additionally, as their understanding of epilepsy grew, so did their sensitivity to those who suffer from the condition. The study also recommends that epilepsy experts deliver additional lectures and training sessions to enhance nurses' knowledge of first-aid for seizures.

Highly sensitive Curcumin-conjugated nanotheranostic platform for detecting amyloid-beta plaques by magnetic resonance imaging and reversing cognitive deficits of Alzheimer's disease via NLRP3-inhibition.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD. RESULTS: Herein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced ß-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of ß-amyloid plaques which more closely revealed real deposition of Aß than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes. CONCLUSIONS: Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.

Comparison of alveolar bone width and sagittal tooth angulation of maxillary central incisors in Class I and Class III canine relationships: a retrospective study using CBCT.

BACKGROUND: Canine relationship is a key reference identifying anterior malocclusion and an important implication for evaluating preimplantation bone morphology at maxillary esthetic zone. This study aimed to compare the differences of maxillary central incisor-related measurements (alveolar bone thickness and tooth sagittal angulation) between Class I and Class III canine relationship and further explore the risk factors for immediate implant placement in the anterior maxilla based on cone beam computed tomography (CBCT) data. METHODS: CBCT digital imaging and communications in medicine (DICOM) files of 107 patients (54 with Class I canine relationship and 53 with Class III canine relationship) were collected and the alveolar bone thickness at mid-root (mid-root buccal thickness/MBT; palatal/MPT), apical regions (apical buccal thickness/ABT; palatal/APT) and sagittal angulation (SA) of the maxillary central incisor at the examined side were measured on the mid-sagittal observation plane. Descriptive statistical analysis and frequency distributions of the measurements based on Class I or Class III canine relationship were established. Statistical analyses were performed using Fisher's exact test, independent samples t test and Pearson correlation test with the significance level set at p < 0.05. RESULTS: The frequency distributions of maxillary central incisors' MPT, ABT, APT and SA showed significant differences between Class I and Class III canine relationships (p = 0.030, 0.024, 0.000 and 0.000, respectively). MPT (2.48 ± 0.88 mm vs. 3.01 ± 1.04 mm, p = 0.005), APT (6.79 ± 1.65 mm vs. 8.47 ± 1.93 mm, p = 0.000) and SA (12.23 ± 5.62° vs. 16.42 ± 4.49°, p = 0.000) were significantly smaller in patients with Class III canine relationship. Moreover, SA showed a strong positive correlation with APT (R = 0.723, p = 0.000) and a moderate negative correlation with ABT (R = - 0.554, p = 0.000). CONCLUSIONS: In populations with Class III canine relationship, maxillary central incisors were significantly more labially inclined and have a thinner palatal bone plate at the apex compared with Class I relationship. Clinicians should avoid palatal perforation during immediate implantation at sites of originally protrusive maxillary incisors.

Role of SIK1 in the transition of acute kidney injury into chronic kidney disease.

BACKGROUND: Acute kidney injury (AKI), with a high morbidity and mortality, is recognized as a risk factor for chronic kidney disease (CKD). AKI-CKD transition has been regarded as one of the most pressing unmet needs in renal diseases. Recently, studies have showed that salt inducible kinase 1 (SIK1) plays a role in epithelial-mesenchymal transition (EMT) and inflammation, which are the hallmarks of AKI-CKD transition. However, whether SIK1 is involved in AKI-CKD transition and by what mechanism it regulates AKI-CKD transition remains unknown. METHODS: We firstly detected the expression of SIK1 in kidney tissues of AKI patients and AKI mice by immunohistochemistry staining, and then we established Aristolochic acid (AA)-induced AKI-CKD transition model in C57BL/6 mice and HK2 cells. Subsequently, we performed immunohistochemistry staining, ELISA, real-time PCR, Western blot, immunofluorescence staining and Transwell assay to explore the role and underlying mechanism of SIK1 on AKI-CKD transition. RESULTS: The expression of SIK1 was down-regulated in AKI patients, AKI mice, AA-induced AKI-CKD transition mice, and HK2 cells. Functional analysis revealed that overexpression of SIK1 alleviated AA-induced AKI-CKD transition and HK2 cells injury in vivo and in vitro. Mechanistically, we demonstrated that SIK1 mediated AA-induced AKI-CKD transition by regulating WNT/ß-catenin signaling, the canonical pathway involved in EMT, inflammation and renal fibrosis. In addition, we discovered that inhibition of WNT/ß-catenin pathway and its downstream transcription factor Twist1 ameliorated HK2 cells injury, delaying the progression of AKI-CKD transition. CONCLUSIONS: Our study demonstrated, for the first time, a protective role of SIK1 in AKI-CKD transition by regulating WNT/ß-catenin signaling pathway and its downstream transcription factor Twist1, which will provide novel insights into the prevention and treatment AKI-CKD transition in the future.

Silica Capsules Templated from Metal-Organic Frameworks for Enzyme Immobilization and Catalysis.

Inspired by the unique biological microenvironments of eukaryotic cells, hollow capsules are promising to immobilize enzymes due to their advantages for physical protection and improved activity of enzymes. Herein, we report a facile method to fabricate silica (SiO2) capsules using zeolitic imidazole framework-8 nanoparticles (ZIF-8 NPs) as templates for enzyme immobilization and catalysis. Enzyme-encapsulated SiO2 capsules are obtained by encapsulation of enzymes in ZIF-8 NPs and subsequent coating of silica layers, followed by the removal of templates in a mild condition (i.e., ethylenediaminetetraacetic acid (EDTA) solution). The enzyme (i.e., horseradish peroxidase, HRP) activity in SiO2 capsules is improved more than 15 times compared to that of enzyme-loaded ZIF-8 NPs. Enzymes in SiO2 capsules maintain a high relative activity after being subjected to high temperature, enzymolysis, and recycling compared to free enzymes. In addition, multienzymes (e.g., glucose oxidase and HRP) can also be coencapsulated within SiO2 capsules to show a reaction with a high cascade catalytic efficacy. This work provides a versatile strategy for enzyme immobilization and protection with potential applications in biocatalysis.

Effect of Elasticity of Silica Capsules on Cellular Uptake.

Understanding the impact of the physicochemical properties of nanoparticles (NPs) on cellular uptake is important to design optimal drug-delivery nanocarriers. Therein, the influence of NP elasticity on bio-nano-interactions remains elusive due to the complexity of factors affecting cellular uptake. Herein, we synthesized SiO2 capsules with tunable elasticity using metal-organic frameworks as templates to investigate their interactions with cells. Young's moduli of the resultant water-filled SiO2 capsules with identical size, shape, composition, and surface charge can be controlled from 3.8 MPa to 4.7 GPa via the variation of capsule shell thickness. As a result, increased elasticity of SiO2 capsules results in higher cellular uptake. Stiff SiO2 capsules have almost 9 times as much cellular uptake as the soft ones. In addition, the elasticity of SiO2 capsules influences cellular uptake pathways, where the clathrin-mediated pathway is preferred for stiff capsules while the uptake of the soft capsules is mostly mediated by a caveolae-dependent pathway. This work confirms the important role of NP elasticity in nonspecific cell interactions, which can provide a foundational understanding for engineering drug-delivery nanocarriers.

Molecular Determination of Organic Adsorption Sites on Smectite during Fe Redox Processes Using ToF-SIMS Analysis.

Turnover of soil organic carbon (SOC) is strongly affected by a balance between mineral protection and microbial degradation. However, the mechanisms controlling the heterogeneous and preferential adsorption of different types of SOC remain elusive. In this work, the heterogeneous adsorption of humic substances (HSs) and microbial carbon (MC) on a clay mineral (nontronite NAu-2) during microbial-mediated Fe redox cycling was determined using time-of-flight secondary ion mass spectrometry (ToF-SIMS). The results revealed that HSs pre-adsorbed on NAu-2 would partially inhibit structural modification of NAu-2 by microbial Fe(III) reduction, thus retarding the subsequent adsorption of MC. In contrast, NAu-2 without precoated HSs adsorbed a significant amount of MC from microbial polysaccharides as a result of Fe(III) reduction. This was attributed to the deposition of a thin Al-rich layer on the clay surface, which provided active sites for MC adsorption. This study provides direct and detailed molecular evidence for the first time to explain the preferential adsorption of MC over HSs on the surface of clay minerals in iron redox processes, which could be critical for the preservation of MC in soil. The results also indicate that ToF-SIMS is a unique tool for understanding complex organic-mineral-microbe interactions.

Comparative Transcriptomic and Proteomic Analyses Prove that IFN-λ1 is a More Potent Inducer of ISGs than IFN-α against Porcine Epidemic Diarrhea Virus in Porcine Intestinal Epithelial Cells.

Type III interferon (IFN-λ) is currently considered to be largely nonredundant to type I interferon (IFN-α) in antivirus infection, especially in epithelial cells. Previous studies reported that, compared with IFN-α, IFN-λ exhibited stronger induction of interferon-stimulated genes (ISGs) at the transcriptional level in intestinal epithelial cells and stronger inhibition of porcine epidemic diarrhea virus (PEDV). In this study, the different mechanisms of ISG upregulation induced by IFN-α and IFN-λ1 were compared at the mRNA and protein levels in the porcine intestinal epithelial cell model (IPEC-J2). It was proved that IFN-λ1 consistently exhibited stronger stimulation effects at both levels. At the mRNA level, 132 genes were significantly upregulated upon IFN-λ1 stimulation, while 42 genes upon IFN-α stimulation. At the protein level, 47 proteins were significantly upregulated upon IFN-λ1 stimulation, but only 8 proteins were upregulated upon IFN-α stimulation. The shared upregulated genes/proteins by IFN-λ1 in both transcriptional and translational omics, especially the regulation factors of ISG15, were involved in the JAK-STAT signaling pathway. Compared to IFN-α, IFN-λ1 could induce more consistent upregulation of the key ISGs (ISG15, USP18, OASL, and RSAD2) at 3-24 h postinduction as measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation. It was further confirmed through functional analysis that ISG15 and RSAD2 could inhibit PEDV infection in dose-dependent manners. This study provided solid evidence that IFN-λ1 could induce a more unique and higher ISG expression level, which exhibited anti-PEDV effects on porcine intestinal epithelial cells.